Autoimmunity is postulated to be a contributing factor in the initiation or perpetuation of several ocular inflammatory disorders. Although the role of autoimmune mechanisms in uveitis is unresolved, it has been shown experimentally that several antigenic preparations of uvea and retina can induce autoimmune uveo-retinitis in several mammalian species. Work in progress here has succeeded in isolating and characterizing two antigens from the outer retina which are involved in pathogenesis: a soluble photoreceptor protein indentified as the primary antigen, and rhodopsin which appears to evoke a mild form of uveitis. We propose to define further the variant forms of disease obtained according to the sensitizing dose, the antigen, and the species immunized, all of which have been found to be important variables in the nature of disease produced. The role of humoral and cellular factors in pathogenesis of disease will be examined by adoptive transfer experiments in inbred animals. Further studies of the apparent heterogeneity of the soluble antigen, and proteolytic fragments of the antigen, will be carried out in order to better identify components having uveitopathogenic activity and those lacking this activity. These approaches will then allow us to explore the role of these components in immune suppression of the disease as a potential therapeutic measure. In addition, the analysis of humoral and cellular responses to pure soluble antigen, and other ocular preparations, of humans with uveo-retinal diseases will be continued in order to examine autoimmune phenomenon in the disorders.